Technical Field
The present invention relates to conjugates between p97 (melanotransferrin) and polynucleotides such as small interfering RNA (siRNA) molecules, and related compositions and methods of use thereof, for instance, to facilitate delivery of siRNA agents across the blood-brain barrier (BBB) and/or improve their tissue penetration in CNS and/or peripheral tissues, and thereby treat and/or diagnose various diseases, including those having a central nervous system (CNS) component.
Description of the Related Art
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. It may be possible to exploit RNA interference in therapy. Although it is difficult to introduce long dsRNA strands into mammalian cells due to the interferon response, the use of short interfering RNA (siRNA) has been more successful.
However, delivery into desired tissues such as tissues of the central nervous system (CNS) presents challenges to the therapeutic use of siRNA molecules. As one problem, the blood-brain barrier (BBB) blocks the free transfer of many agents from blood to brain. For this reason, diseases that present with significant neurological aspect are not expected to be as responsive to routine routes of administration such as IV or subcutaneous administration. For such diseases and others, methods of improving the delivery of the siRNA molecules across the BBB would be highly desirable.